Interferon-γ protects against herpes simplex virus type 1-mediated neuronal death

Kathrin D. Geiger, Therese C. Nash, Stephen Sawyer, Troy Krahl, Gail Patstone, John C. Reed, Stan Krajewski, Dyana Dalton, Michael J. Buchmeier, Nora Sarvetnick

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

Host inflammatory mediators, such as interferons, play a protective role in infection, but the mechanism is undefined and may differ between tissue compartments. To determine whether interferon-γ (IFN-γ) elicitation prevents destructive encephalitis in herpes simplex virus type 1 (HSV-1) infection of the central nervous system, IFN-γ-knockout (GKO) mice were challenged intravitreally with HSV-1 strain F, inciting infection of the eyes and the brain. Indeed, the GKO mice showed encephalitis with ataxia, whereas nontransgenic controls remained asymptomatic. Morphology and digoxigenin labeling of DNA fragments revealed increased apoptosis in the brains of GKO mice compared with controls, although vital replication was not influenced at early stages of infection. Greater numbers of apoptotic cells in the brains of GKO mice correlated with neurological symptoms, as well as lower expression of the protective protooncogene bcl-2. Thus, IFN-γ inhibits apoptosis, affording neuronal protection from destructive encephalitis during viral infection of the central nervous system.

Original languageEnglish (US)
Pages (from-to)189-197
Number of pages9
JournalVirology
Volume238
Issue number2
DOIs
StatePublished - Nov 24 1997
Externally publishedYes

ASJC Scopus subject areas

  • Virology

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